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Objectives There is growing interest in condition-specific preference measures, including the European Organisation for Research and Treatment of Cancer Quality of Life Utility Measure-Core 10 Dimensions (QLU-C10D). This research assessed the implications of using utility indices on the basis of the EQ-5D-3L, a mapping of EQ-5D-3L to the EQ-5D-5L, and the QLU-C10D, and compared their psychometric properties. Methods Data were taken from 8 phase 3 randomized controlled trials of nivolumab with or without ipilimumab for the treatment of solid tumors. Utilities for progression-related states were calculated using the UK and English value sets and incremental quality-adjusted life-years (QALYs) derived from established UK cost-effectiveness models. The psychometric properties of the utility indices were assessed using pooled trial data. Results Compared with the EQ-5D-3L index, the mapped EQ-5D-5L index yielded an average of 6% more and the QLU-C10D index an average of 2% fewer incremental QALYs for nivolumab versus comparators. All indices could differentiate between groups defined by performance status, cancer stage, or self-reported health status at baseline and detect meaningful changes in performance status, tumor response, health status, and quality of life over approximately 12 weeks of treatment. Conclusions The lower QALY yield of the QLU-C10D was balanced by evidence of greater validity and responsiveness. Benefits gained from using the QLU-C10D may be apparent when treatments affect targeted symptoms and functional aspects, including sleep, bowel function, appetite, nausea, and fatigue. The observed differences in QALYs may not be sufficiently large to affect health technology assessment decisions.

Objectives The original 3-level EQ-5D (EQ-5D-3L) includes 5 dimensions with 3 levels of problems per dimension. Since 2010, a more sensitive version with 5 levels of problems per dimension (EQ-5D-5L) has become available. Population value sets have been developed for both versions of the questionnaire. The objective of this research was to develop a mapping function to link EQ-5D-3L responses to value sets for the EQ-5D-5L. Methods Various algorithms were developed to link EQ-5D-3L and EQ-5D-5L responses using data from an observational study including members of 10 subgroups (N = 3580) who completed both versions of the questionnaire. Nonparametric and ordinal logistic regression models were fit to the data and compared using Akaike’s information criterion (AIC) as well as the mean absolute error and root mean squared error of predictions. Results were contrasted qualitatively and quantitatively with those of an alternative copula-based approach. Results Including indicants of problems for other EQ-5D-3L dimensions as regressors in the modeling yielded the greatest improvement in prediction accuracy. Adding age and gender lowered the AIC without improving predictions, while including a latent factor lowered the AIC further and slightly improved predictive accuracy. Models that conditioned on problems in other EQ-5D-3L dimensions yielded more accurate predictions than the alternative copula-based approach in subgroups defined by age and gender. Conclusion We present novel algorithms to map EQ-5D-3L responses to EQ-5D-5L value sets. The recommended approach is based on an ordinal logistic regression that disregards age and gender and accounts for unobserved heterogeneity using a latent factor.

Introduction Discrete choice experiments (DCE) are increasingly being conducted using online panels. However, the comparability of such DCE-based preferences to traditional modes of data collection (e.g., in-person) is not well established. In this study, supervised, face-to-face DCE was compared with its unsupervised, online facsimile on face validity, respondent behavior, and modeled preferences. Methods Data from face-to-face and online EQ-5D-5L health state valuation studies were compared, in which each used the same experimental design and quota sampling procedure. Respondents completed 7 binary DCE tasks comparing 2 EQ-5D-5L health states presented side by side (health states A and B). Data face validity was assessed by comparing preference patterns as a function of the severity difference between 2 health states within a task. The prevalence of potentially suspicious choice patterns (i.e., all As, all Bs, and alternating As/Bs) was compared between studies. Preference data were modeled using multinomial logit regression and compared based on dimensional contribution to overall scale and importance ranking of dimension-levels. Results One thousand five Online respondents and 1,099 face-to-face screened (F2FS) respondents were included in the main comparison of DCE tasks. Online respondents reported more problems on all EQ-5D dimensions except for Mobility. The face validity of the data was similar between comparators. Online respondents had a greater prevalence of potentially suspicious DCE choice patterns ([Online]: 5.3% [F2FS] 2.9%, P = 0.005). When modeled, the relative contribution of each EQ-5D dimension differed between modes of administration. Online respondents weighed Mobility more importantly and Anxiety/Depression less importantly. Discussion Although assessments of face validity were similar between Online and F2FS, modeled preferences differed. Future analyses are needed to clarify whether differences are attributable to preference or data quality variation between modes of data collection.

Aim The EQ-5D is a generic measure of health that is widely applied for health economic and non-economic purposes. Population norms can be used to facilitate the interpretation of EQ-5D data. The objective of this study was to develop a set of pooled normative EQ-5D-3L values for the five largest European economies (EUR5). Methods EQ-5D-3L index values based on the time trade-off (TTO) were available for all EUR5 countries (n = 21,425): France, Germany, Italy, Spain, and the United Kingdom (UK). Country-specific data sets were aggregated and weighted to facilitate the derivation of norms for gender and age groups. Analyses included equal weighting and weighting by population and economy size. Norms were also calculated using the European visual analog scale-based value set (European VAS), the EQ VAS and separately by dimension. Results Pooled mean (SD) population weighted TTO values for males/females were 0.967 (0.122)/0.959 (0.118) for ages 18–24; 0.965 (0.096)/0.954 (0.117) for ages 25–34; 0.943 (0.165)/0.936 (0.169) for ages 35–44; 0.934 (0.150)/0.921 (0.157) for ages 45–54; 0.896 (0.188)/0.875 (0.197) for ages 55–64; 0.900 (0.158)/0.839 (0.218) for ages 65–74; and 0.830 (0.234)/0.756 (0.291) for ages 75 and older. Mean values decreased and variance increased with age; females had slightly lower mean values than males across all age bands. The unequal weighting approaches produced similar point estimates with smaller variances. Mean values for the European VAS were slightly lower than those for the TTO-based index. Discussion Normative EQ-5D-3L values can be used to benchmark the outcomes of treated patients against the health of the general population. EUR5 norms may be useful in research applications inferring to Europe or the European Union as a whole, particularly when sample size precludes analysis at the country level.

Objective The aim of this study was to compare online, unsupervised and face-to-face (F2F), supervised valuation of EQ-5D-5L health states using composite time trade-off (cTTO) tasks. Methods The official EuroQol experimental design and valuation protocol for the EQ-5D-5L of 86 health states were implemented in interviewer-assisted, F2F and unsupervised, online studies. Validity of preferences was assessed using prevalence of inconsistent valuations and expected patterns of TTO values. Respondent task engagement was measured using number of trade-offs and time per task. Trading patterns such as better-than-dead only was compared between modes. Value sets were generated using linear regression with a random intercept (RILR). Value set characteristics such as range of scale and dimension ranking were evaluated between modes. Results Five hundred one online and 1,134 F2F respondents completed the surveys. Mean elicited TTO values were higher online than F2F when compared by health state severity. Compared to F2F, a larger proportion of online respondents did not assign the poorest EQ-5D-5L health state (i.e., 55555) the lowest TTO value ([Online] 41.3% [F2F] 12.2%) (p p Conclusions Compared to F2F data, TTO tasks conducted online had more inconsistencies and decreased engagement, which contributed to compromised data quality. This study illustrates the challenges of conducting online valuation studies using the TTO approach.

Purpose The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core Questionnaire (QLQ-C30) is a widely used generic self-report measure of health-related quality of life (HRQOL) for cancer patients. However, no validated voice script for interviewer-led telephone administration was previously available. The aim of this study was to develop a voice script for interviewer administration via telephone. Methods Following guidelines from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) PRO Mixed Modes Good Research Practices Task Force, a randomised cross-over equivalence study, including cognitive debriefing, was conducted to assess equivalence between paper and telephone administration modes. Assuming an expected intraclass correlation coefficient (ICC) of 0.70 and a minimally acceptable level of 0.50, a sample size of 63 was required. Results Cognitive interviews with five cancer patients found the voice script to be clear and understandable. Due to a protocol deviation in the first wave of testing, only 26 patients were available for analyses. A second wave of recruitment was conducted, adding 37 patients (n = 63; mean age 55.48; 65.1% female). Total ICCs for mode comparison ranged from 0.72 (nausea and vomiting, 95% CI 0.48–0.86) to 0.90 (global health status/QoL, 95% CI 0.80–0.95; pain, 95% CI 0.79–0.95; constipation, 95% CI 0.80–0.95). For paper first administration, all ICCs were above 0.70, except nausea and vomiting (ICC 0.55; 95% CI 0.24–0.76) and financial difficulties (ICC 0.60; 95% CI 0.31–0.79). For phone first administration, all ICCs were above 0.70. Conclusions The equivalence testing results support the voice script’s validity for administration of the QLQ-C30 via telephone.

Web-based surveys are increasingly utilized for health valuation studies but may be more prone to lack of engagement and, therefore, poor data validity. The objective of this study was to evaluate the effect of imposed engagement (i.e., at least three trade-offs) in the composite time trade-off (cTTO) task. The EQ-5D-5L valuation study protocol and study design were adapted for online, unsupervised completion in two arms: base case and engagement. Validity of preferences was assessed using the prevalence of inconsistent valuations and expected patterns of TTO values. Respondent task engagement was measured using time per task. Value sets were generated using linear regression with a random intercept (RILR). The base case (n = 501) and engagement arms (n = 504) clustered at different TTO values: [base case] 0, 1; [engagement] -0.5, 0.45, 0.6. Mean TTO values were lower for the engagement arm. Engagement respondents did not spend more time per TTO task: [base case] 63.3 s (SD 77.9 s); [engagement] 64.7 s (SD 73.3 s); p = 0.36. No significant difference was found between arms for prevalence of respondents with at least one inconsistent TTO value: [base case] 61.1%; [engagement] 63.5%; p = 0.43. Both value sets had significant intercepts far from 1: [base case] 0.846; [engagement] 0.783. The relative importance of the EQ-5D dimensions also differed between arms. Both online arms had poor quality data. A minimum trade-off threshold did not improve engagement nor face validity of the data, indicating that modifications to the number of iterations are insufficient alone to improve data quality/validity of online TTO studies.

To evaluate the influence of recall periods on the assessment of physical function, we compared, in cancer and general population samples, the standard administration of PROMIS Physical Function items without a recall period to administrations with 24-hour and 7-day recall periods. We administered 31 items from the PROMIS Physical Function v2.0 item bank to 2400 respondents (n = 1001 with cancer; n = 1399 from the general population). Respondents were randomly assigned to one of three recall conditions (no recall, 24-hours, or 7-days) and one of two “reminder” conditions (with recall periods presented only at the start of the survey or with every item). We assessed items for potential differential item functioning (DIF) by recall time period. We then tested recall and reminder effects with analysis of variance controlling for demographics, English fluency, and co-morbidities. Based on conservative pre-set criteria, no items were flagged for recall time period-related DIF. Using analysis of variance, each condition was compared to the standard PROMIS administration for Physical Function (no recall period). There was no evidence of significant differences among groups in the cancer sample. In the general population sample, only the 24-hour recall condition with reminders was significantly different from the “no recall” PROMIS standard. At the item level, for both samples, the number of items with non-trivial effect size differences across conditions was minimal. Compared to no recall, the use of a recall period has little to no effect upon PROMIS physical function responses or scores. We recommend that PROMIS Physical Function be administered with the standard PROMIS “no recall” period.

Background The EORTC QLU-C10D is a multiattribute utility measure derived from the cancer-specific quality-of-life questionnaire, the EORTC QLQ-C30. The QLU-C10D contains 10 dimensions (physical, role, social and emotional functioning, pain, fatigue, sleep, appetite, nausea, bowel problems). The objective of this study was to develop a United States value set for the QLU-C10D. Methods A US online panel was quota recruited to achieve a representative sample for sex, age (≥18 y), race, and ethnicity. Respondents undertook a discrete choice experiment, each completing 16 choice-pairs, randomly assigned from a total of 960 choice-pairs. Each pair included 2 QLU-C10D health states and duration. Data were analyzed using conditional logistic regression, parameterized to fit the quality-adjusted life-year framework. Utility weights were calculated as the ratio of each dimension-level coefficient to the coefficient for life expectancy. Results A total of 2480 panel members opted in, 2333 (94%) completed at least 1 choice-pair, and 2273 (92%) completed all choice-pairs. Within dimensions, weights were generally monotonic. Physical functioning, role functioning, and pain were associated with the largest utility weights. Cancer-specific dimensions, such as nausea and bowel problems, were associated with moderate utility decrements, as were general issues such as problems with emotional functioning and social functioning. Sleep problems and fatigue were associated with smaller utility decrements. The value of the worst health state was 0.032, which was slightly greater than 0 (equivalent to being dead). Conclusions This study provides the US-specific value set for the QLU-C10D. These estimated health state scores, based on responses to the EORTC QLQ-C30 questionnaire, can be used to evaluate the cost-utility of oncology treatments.

Objectives In the CheckMate 141 trial (NCT02105636), nivolumab demonstrated survival, health-related quality of life, and healthcare resource utilization benefits vs single-agent therapy of investigator’s choice (IC) (methotrexate, docetaxel or cetuximab) in patients with platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). We assessed between-treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST). Methods Survival data from CheckMate 141 (nivolumab, n = 240; IC, n = 121) was partitioned into toxicity (TOX), time without symptoms or toxicity (TWiST), and relapse (REL). TOX was defined as time spent with all-cause grade 3–4 adverse events after randomization, before disease progression. TWiST was defined as time not in TOX or REL. REL was defined as time between disease progression and death. Utility values derived from three-level EuroQol five-dimensional questionnaire data from CheckMate 141 were used to calculate Q-TWiST as the utility-weighted sum of the mean duration in each health state. Results The between-group difference in Q-TWiST score was 1.23 months (95% confidence interval 1.17–1.29) favoring nivolumab (p 10%) in quality-adjusted survival vs standard of care in patients with R/M SCCHN.

Objectives The introduction of innovative, high-cost oncology treatments, coupled with mounting budgetary pressures, necessitates value trade-offs across cancer types. Defining value is critical to informing decision-making. A cost-value analysis tool was used to assess relative clinical value from a US perspective using multiple outcome metrics for a variety of metastatic cancers. Methods Literature published (January 1, 2000-August 31, 2016) was reviewed to identify outcome metrics for approved treatments for metastatic cancers. Data were extracted or derived for median and mean overall survival (OS), landmark survival rates, and other survival metrics, and compared across treatments vs their respective trial comparators, with and without considering costs. Results Reported survival metrics varied by agent within cancer type. For treatment of prostate cancer, abiraterone yielded the highest improvement in 1-year survival rate (13.7%, previously treated), whereas enzalutamide yielded the highest median OS improvement (4.8 months, previously treated) and sipuleucel-T, the highest mean OS improvement (3.6 months, previously untreated) vs their respective trial comparators. For treatment of non-small cell lung cancer vs their respective trial comparators, nivolumab yielded the highest improvement in mean OS (11.9 months) and 3-year survival rate (12.6%), each in previously treated squamous disease, whereas afatinib yielded the highest median OS improvement (4.1 months, previously untreated EGFR del19 and L858R mutants). Cost-value analysis results varied with the applied survival metric. Conclusions Although median OS is the traditional gold standard oncology efficacy metric, it fails to capture long-term survival benefits-the ultimate goal of cancer treatment-offered by new treatment modalities. Diverse metrics are needed for comprehensive value assessments of cancer therapies.

Objective To derive a US-based value set for the EQ-5D-5L questionnaire using an international, standardized protocol developed by the EuroQol Group. Methods Respondents from the US adult population were quota-sampled on the basis of age, sex, ethnicity, and race. Trained interviewers guided participants in completing composite time trade-off (cTTO) and discrete choice experiment (DCE) tasks using the EuroQol Valuation Technology software and routine quality control measures. Data were modeled using a Tobit model for cTTO data, a mixed logit model for DCE data, and a hybrid model that combined cTTO and DCE data. Model performance was compared on the basis of logical ordering of coefficients, statistical significance, parsimony, and theoretical considerations. Results Of 1134 respondents, 1062, 1099, and 1102 respondents provided useable cTTO, DCE, and cTTO or DCE responses, respectively, on the basis of quality control criteria and interviewer judgment. Respondent demographic characteristics and health status were similar to the 2015 US Census. The Tobit model was selected as the preferred model to generate the value set. Values ranged from −0.573 (55 555) to 1 (11 111), with 20% of all predicted health states scores less than 0 (ie, worse than dead). Conclusions A societal value set for the EQ-5D-5L was developed that can be used for economic evaluations and decision making in US health systems. The internationally established, standardized protocol used to develop this US-based value set was recommended by the EuroQol Group and can facilitate cross-country comparisons.

Purpose The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core Questionnaire (QLQ-C30) is a widely used generic self-report measure of health-related quality of life (HRQOL) for cancer patients. However, no validated voice script for interviewer-led telephone administration was previously developed that could be used as an alternative to self-completion. The aim of this study was to develop a voice script for interviewer administration via telephone. Methods Following guidelines from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) PRO Mixed Modes Good Research Practices Task Force, a randomised cross-over equivalence study, including cognitive debriefing, was conducted to assess equivalence between paper and telephone administration modes. Assuming an expected intraclass correlation coefficient (ICC) of 0.70 and a minimally acceptable level of 0.50, a sample size of 63 was required. Results Cognitive interviews with five cancer patients found the voice script to be clear and understandable. Due to a protocol deviation in the first wave of testing, only 26 patients were available for analyses. A second wave of recruitment was conducted, adding 37 patients (n=63; mean age 55.48; 65.1% female). ICCs for mode comparison ranged from 0.72 (nausea and vomiting, 95% CI 0.48-0.86) to 0.90 (global health status/QoL, 95% CI 0.80-0.95; pain, 95% CI 0.79-0.95; constipation, 95% CI 0.80-0.95). For paper versus phone, all ICCs were above 0.70, except nausea and vomiting (95% CI 0.55). For phone versus paper, all ICCs were above 0.70. Conclusions The equivalence testing results support the voice script’s validity for administration of the QLQ-C30 via telephone.

It is important that patient-reported outcome (PRO) measures used to assess cancer therapies adequately capture the benefits and risks experienced by patients, particularly when adverse event profiles differ across therapies. This study explores the case for augmenting preference-based utility measures to capture the impact of cancer treatment-related symptoms. Additional cancer treatment-related items could be specific (e.g., rash) or global. While specific items are easier to describe and understand, their use may miss rarer symptoms and those that are currently unknown but will arise from future medical advancements. The appropriate number of additional items, the independence of those items, and their impact on the psychometric properties of the core instrument require consideration. Alternatively, a global item could encompass all potential treatment-related symptoms, of any treatments for any disease. However, such an item may not be well understood by general public respondents in valuation exercises. Further challenges include the decision about whether to generate de novo value sets for the modified instrument or to map to existing tariffs. The fluctuating and transient nature of treatment-related symptoms may be inconsistent with the methods used in conventional valuation exercises. Fluctuating symptoms could be missed by sub-optimal measure administration timing. The addition of items also poses double-counting risks. In summary, the addition of treatment-related symptom items could increase the sensitivity of existing utility measures to capture known and unknown treatment effects in oncology, while retaining the core domains. However, more research is needed to investigate the challenges, particularly regarding valuation.

Aim: To assess the cost-effectiveness of nivolumab monotherapy for recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) in the US. Methods: We constructed a cohort-based partitioned survival model for three health states (progression-free, progressed disease, and death). Using overall survival and progression-free survival data from the nivolumab and investigator’s choice (IC) arms of the CheckMate 141 study, the proportion of patients in each health state was estimated by parametric modeling over a 25-year period. Cost, utility, adverse event, and disease management data inputs were obtained from relevant literature and applied to patients in each health state. A scenario analysis was conducted assuming increased uptake of subsequent immunotherapies. A one-way deterministic sensitivity analysis assessed the impact of variation in multiple parameters. A probabilistic sensitivity analysis in which probabilistic distributions were applied to each input during 1,000 model iterations was also conducted. Results: Total costs incurred were higher with nivolumab ($101,552) than with IC ($38,067). Nivolumab was associated with a higher number of life-years (LY; 1.21) and quality-adjusted life-years (QALYs; 0.89), compared with IC (0.68 and 0.42, respectively). The incremental cost-effectiveness ratio for nivolumab compared with IC was $134,438 per QALY, and this remained qualitatively similar when increased uptake of subsequent immunotherapies was assumed ($129,603 per QALY). Sensitivity analyses supported these findings. Conclusions: These results suggest that, at a willingness-to-pay threshold of $150,000 per QALY, nivolumab is a cost-effective option for therapy of SCCHN in the US.

Background Incorporating patient reporting of symptomatic adverse events (AEs) is important in evaluating safety and tolerability in cancer clinical trials. The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to assess the frequency, severity, and/or interference of patient-reported symptomatic AEs. The objective of this study was to identify, based on oncologist and patient interviews, a relevant subset of symptomatic AEs from the PRO-CTCAE that can be used to optimize patient reporting of symptomatic AEs in hepatocellular carcinoma (HCC) clinical trials. Methods Qualitative and quantitative data on HCC diagnosis, treatment, symptoms, and side effects were collected from patients. Using a numerical rating scale, medical oncologists specializing in HCC rated the importance of (1) 34 symptomatic AEs (Grade ≥2) identified in past sponsor HCC clinical trials, (2) each PRO-CTCAE symptomatic AE item to the patient, and (3) each PRO-CTCAE symptomatic AE item with respect to patient safety or tolerability. Patients completed the PRO-CTCAE items and were debriefed on the importance of each PRO-CTCAE symptomatic AE to them. Results Five medical oncologists from the United States, Spain, Taiwan, Korea, and Hong Kong with 14 to 30 years of experience, and 17 patients with HCC and Child-Pugh class A or B cirrhosis status completed interviews. Medical oncologists rated the following symptomatic AEs from prior trials as being highly important to patients (mean rating of ≥7 on a scale from 0 to 10): hand-foot syndrome, diarrhea, fatigue, decreased appetite, rash, vomiting, and weight loss. PRO-CTCAE symptomatic AEs rated by medical oncologists as being highly important to patients included diarrhea, vomiting, shivering or shaking chills, hand-foot syndrome, rash, fatigue, difficulty swallowing, decreased appetite, and loss of control of bowel movements. Patients rated the following PRO-CTCAE symptomatic AEs as being highly important: loss of appetite/lack of interest in food, pain/tenderness at injection/insertion site, fatigue/lack of energy/tiredness, nausea, and hair loss. Conclusions This study identified a preliminary list of clinically relevant symptomatic AEs from interviews with both medical oncologists and patients that can be used to support assessments of treatment safety and tolerability in HCC clinical trials.

PURPOSE: To evaluate the influence of recall periods on the assessment of physical function, we compared, in cancer and general population samples, the standard administration of PROMIS Physical Function items without a recall period to administrations with 24-hour and 7-day recall periods. METHODS: We administered 31 items from the PROMIS Physical Function v2.0 item bank to 2400 respondents (n = 1001 with cancer; n = 1399 from the general population). Respondents were randomly assigned to one of three recall conditions (no recall, 24-hours, or 7-days) and one of two “reminder” conditions (with recall periods presented only at the start of the survey or with every item). We assessed items for potential differential item functioning (DIF) by recall time period. We then tested recall and reminder effects with analysis of variance controlling for demographics, English fluency, and co-morbidities. RESULTS: Based on conservative pre-set criteria, no items were flagged for recall time period-related DIF. Using analysis of variance, each condition was compared to the standard PROMIS administration for Physical Function (no recall period). There was no evidence of significant differences among groups in the cancer sample. In the general population sample, only the 24-hour recall condition with reminders was significantly different from the “no recall” PROMIS standard. At the item level, for both samples, the number of items with non-trivial effect size differences across conditions was minimal. CONCLUSIONS: Compared to no recall, the use of a recall period has little to no effect upon PROMIS physical function responses or scores. We recommend that PROMIS Physical Function be administered with the standard PROMIS “no recall” period.

Aims: In 2016, nivolumab and pembrolizumab were approved for the treatment of squamous cell carcinoma of the head and neck (SCCHN) following progression after initial platinum-based therapy. We sou...

Summary Background Patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck have few treatment options and poor prognosis. Nivolumab significantly improved survival of this patient population when compared with standard single-agent therapy of investigator's choice in Checkmate 141; here we report the effect of nivolumab on patient-reported outcomes (PROs). Methods CheckMate 141 was a randomised, open-label, phase 3 trial in patients with recurrent or metastatic squamous cell carcinoma of the head and neck who progressed within 6 months after platinum-based chemotherapy. Patients were randomly assigned (2:1) to nivolumab 3 mg/kg every 2 weeks (n=240) or investigator's choice (n=121) of methotrexate (40–60 mg/m 2 of body surface area), docetaxel (30–40 mg/m 2 ), or cetuximab (250 mg/m 2 after a loading dose of 400 mg/m 2 ) until disease progression, intolerable toxicity, or withdrawal of consent. On Jan 26, 2016, the independent data monitoring committee reviewed the data at the planned interim analysis and declared overall survival superiority for nivolumab over investigator's choice therapy (primary endpoint; described previously). The protocol was amended to allow patients in the investigator's choice group to cross over to nivolumab. All patients not on active therapy are being followed for survival. As an exploratory endpoint, PROs were assessed at baseline, week 9, and every 6 weeks thereafter using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire–Core 30 (QLQ-C30), the EORTC head and neck cancer-specific module (EORTC QLQ-H&N35), and the three-level European Quality of Life–5 Dimensions (EQ-5D) questionnaire. Differences within and between treatment groups in PROs were analysed by ANCOVA among patients with baseline and at least one other assessment. All randomised patients were included in the time to clinically meaningful deterioration analyses. Median time to clinically meaningful deterioration was analysed by Kaplan-Meier methods. CheckMate 141 was registered with ClinicalTrials.org, number NCT02105636. Findings Patients were enrolled between May 29, 2014, and July 31, 2015, and subsequently 361 patients were randomly assigned to receive nivolumab (n=240) or investigator's choice (n=121). Among them, 129 patients (93 in the nivolumab group and 36 in the investigator's choice group) completed any of the PRO questionnaires at baseline and at least one other assessment. Treatment with nivolumab resulted in adjusted mean changes from baseline to week 15 ranging from −2·1 to 5·4 across functional and symptom domains measured by the EORTC QLQ-C30, with no domains indicating clinically meaningful deterioration. By contrast, eight (53%) of the 15 domains in the investigator's choice group showed clinically meaningful deterioration (10 points or more) at week 15 (change from baseline range, −24·5 to 2·4). Similarly, on the EORTC QLQ-H&N35, clinically meaningful worsening at week 15 was seen in no domains in the nivolumab group and eight (44%) of 18 domains in the investigator's choice group. Patients in the nivolumab group had a clinically meaningful improvement (according to a difference of 7 points or greater) in adjusted mean change from baseline to week 15 on the EQ-5D visual analogue scale, in contrast to a clinically meaningful deterioration in the investigator's choice group (7·3 vs −7·8). Differences between groups were significant and clinically meaningful at weeks 9 and 15 in favour of nivolumab for role functioning, social functioning, fatigue, dyspnoea, and appetite loss on the EORTC QLQ-C30 and pain and sensory problems on the EORTC QLQ-H&N35. Median time to deterioration was significantly longer with nivolumab versus investigator's choice for 13 (37%) of 35 domains assessed across the three questionnaires. Interpretation In this exploratory analysis of CheckMate 141, nivolumab stabilised symptoms and functioning from baseline to weeks 9 and 15, whereas investigator's choice led to clinically meaningful deterioration. Nivolumab delayed time to deterioration of patient-reported quality-of-life outcomes compared with single-agent therapy of investigator's choice in patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck. In view of the major unmet need in this population and the importance of maintaining or improving quality of life for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, these data support nivolumab as a new standard-of-care option in this setting. Funding Bristol-Myers Squibb.

To compare self-rated health among the United States general population in 2002 and 2017. Secondary data were analyzed from two EQ-5D valuation studies conducted in 2002 and 2017. Both studies included the EQ-5D-3L self-classifier and visual analog scale (VAS), where health is rated from 0 (worst imaginable health) to 100 (best imaginable health). VAS scores were compared between time points using regression models, adjusting for sociodemographic factors (Model 1), plus illness (Model 2), and health problems according to the EQ-5D classifier (Model 3). Mean VAS scores in 2002 [84.4 (SD = 16.1)] were not different from 2017 [84.6 (SD = 14.5)] (p = 0.63), nor different after adjusting for demographics (Model 1) or illness (Model 2). However, 2017 VAS mean scores were significantly higher than 2002 [2.2 (95% CI 1.36–3.10)] upon adjusting for the presence of dimension-specific health problems. Self-rated health of the general US adult population in 2017 was similar to 2002, but after adjusting for health problems, scores were slightly higher in 2017. Sociodemographic shifts in age and education explain some of the differences in scores, and by removing health and sociodemographic factors, we found the VAS reveals self-rated health is slightly better in 2017 than 2002.

In the present study, we examined real-world treatment patterns for squamous cell carcinoma of the head and neck (scchn) in Canada, which are largely unknown. Oncologists across Canada provided data for disease history, characteristics, and treatment patterns during May&ndash, July 2016 for 6&ndash, 8 consecutive patients receiving first-line or second-line drug treatment for scchn (including locally advanced and recurrent or metastatic disease). Information from 16 physicians for 109 patients receiving drug treatment for scchn was provided, 1 patient was excluded from the treatment-pattern analysis. Median age in the cohort was 63 years [interquartile range (iqr): 57&ndash, 68 years], and 24% were current smokers, with a mean exposure of 26.2 &plusmn, 12.7 pack&ndash, years. The most common tumour site was the oropharynx (48%). Most patients (84%) received platinum-based regimens as first-line treatment (44% received cisplatin monotherapy). Use of cetuximab-based regimens as first-line treatment was limited (17%). Of 53 patients receiving second-line treatment, 87% received a first-line platinum-based regimen. Median time between first-line treatment with a platinum-based regimen and initiation of second-line treatment was 55 days (iqr: 20&ndash, 146 days). The most common second-line regimen was cetuximab monotherapy (43%), platinum-based regimens were markedly infrequent (13%). Our analysis provides real-world insight into scchn clinical practice patterns in Canada, which could inform reimbursement decision-making. High use of platinum-based regimens in first-line drug treatment was generally reflective of treatment guidelines, cetuximab use in the second-line was higher than anticipated. Additional real-world studies are needed to understand the effect of novel therapies such as immuno-oncology agents on clinical practice and outcomes, particularly for recurrent or metastatic scchn.

Patients with recurrent or metastatic cancer commonly suffer from debilitating toxicity associated with conventional treatment modalities, as well as disease-related symptoms, often with a concomitant negative impact on health-related quality of life (HRQoL). Patient-reported outcomes (PROs) provide important insights into the patient experience in clinical trials. Nivolumab is a programmed death-1 receptor inhibitor that extends survival in patients with recurrent or metastatic disease in multiple tumor types. In this review, we summarize published PRO analyses from eight phase II-IV clinical trials with nivolumab for the treatment of melanoma, non-small cell lung cancer, renal cell carcinoma (RCC), and squamous cell carcinoma of the head and neck (SCCHN). Symptom burden, physical functioning, and HRQoL were measured using generic, cancer-specific, and tumor type-specific validated PRO instruments. Nivolumab showed sustained stabilization across all tumor types and, in some cases, clinically meaningful improvement in HRQoL, whereas standard of care therapies often led to deteriorations. Exploratory analyses found a positive correlation between baseline HRQoL scores and overall survival in RCC, and between baseline HRQoL scores and healthcare resource utilization in SCCHN, suggesting that patient-reported symptoms at treatment initiation may have clinical value. In the era of value-based oncology care, stakeholders are increasingly interested in PRO findings to guide clinical, regulatory, and reimbursement decisions. However, missing data remain a significant challenge in PRO analyses, including in nivolumab trials. Future clinical trials in immuno-oncology should incorporate PRO data collection, including beyond treatment discontinuation or trial completion to assess the long-term effects of treatment on HRQoL.

OBJECTIVE Children with JIA have long-term morbidity and require extensive parental assistance. This study aimed to evaluate the impact of having a child with JIA on parents' missed work time, which can lead to decreased work productivity. METHODS The Truven Health MarketScan Commercial Database (2000-9) was accessed to identify a cohort of parents having a child with newly diagnosed JIA. For comparison, a cohort of parents having no children with JIA was identified and matched with the preceding cohort. Parents' work absences were analysed using descriptive statistics and multivariable regression. Estimates were weighted to be generalizable to the US employer-sponsored insurance population. RESULTS The study identified 108 parents having a child with newly diagnosed JIA (mean age 42.5 years), representing an estimated 3335 (weighted) parents nationally. Most of them were from the South (45%), male (71%) and employed in the transportation and utilities industry (58%). The demographic characteristics of the control cohort of parents were generally similar. Children with JIA (mean age 10.6 years) represented an estimated 3528 cases nationally. The mean number of reported missed work-time hours was 281.81 (s.e. 40.50) in a 9 year period for parents having a child with JIA compared with other parents 183.36 (28.55). Work-time loss was significantly related to having a child with JIA, sex and geographical region of residence. Parents having a child with JIA were 2.78 times more likely to report work-time loss [odds ratio (OR) 2.78 (95% CI 1.47, 5.26)] than those having no children with JIA. CONCLUSION Parents having a child with JIA report significant work-time loss compared with parents with no children having JIA, particularly during the year following the child's diagnosis.

Objective: To assess the QoL reported by GBM patients and their caregivers METHODOLOGY: Real-world data were collected through a cross-sectional survey administered to physicians, patients, and caregivers in France, Germany, and the UK between May and July 2016. Physicians confirmed diagnosis and assessed patients as having progressed, being stable, or responding to treatment. Patient-reported outcomes (PROs) were measured using the 3-level EQ-5D as well as the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and brain cancer-specific module (QLQ-BN20). For patients who could not complete the EQ-5D, proxy assessments were obtained from caregivers. Summary statistics were reported and differences were assessed using pairwise t tests. Results: A total of 313 GBM patients completed the PRO measures, while 203 caregivers provided a proxy EQ-5D assessment. Patient QoL was poor as indicated by a mean (SD) EQ-5D index score of 0.51 (0.38). Significant differences were observed among patient groups defined according to progression. Those whose disease had progressed had a mean (SD) index score of 0.26 (0.38) compared with 0.53 (0.37 p

OBJECTIVE To assess the impact of rheumatoid arthritis (RA) on absence time, absence payments, and other health benefit costs from the perspective of US employers. METHODS Retrospective regression-controlled analysis of a database containing US employees' administrative health care and payroll data for those who were enrolled for at least 1 year in an employer-sponsored health insurance plan. RESULTS Employees with RA (N = 2705) had $4687 greater average annual medical and prescription drug costs (P < 0.0001) and $525 greater (P < 0.05) indirect costs (because of sick leave, short- and long-term disability, and workers' compensation absences) than controls (N = 338,035). Compared with controls, the employees with RA used an additional 3.58 annual absence days, including 1.2 more sick leave and 1.91 more short-term disability days (both P < 0.0001). CONCLUSION Employees with RA have greater costs across all benefits than employees without RA.

Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition.In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life.The median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to 6.0) in the group that received standard therapy. Overall survival was significantly longer with nivolumab than with standard therapy (hazard ratio for death, 0.70; 97.73% CI, 0.51 to 0.96; P=0.01), and the estimates of the 1-year survival rate were approximately 19 percentage points higher with nivolumab than with standard therapy (36.0% vs. 16.6%). The median progression-free survival was 2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to 3.1) with standard therapy (hazard ratio for disease progression or death, 0.89; 95% CI, 0.70 to 1.13; P=0.32). The rate of progression-free survival at 6 months was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was 13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the nivolumab group versus 35.1% of those in the standard-therapy group. Physical, role, and social functioning was stable in the nivolumab group, whereas it was meaningfully worse in the standard-therapy group.Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy. (Funded by Bristol-Myers Squibb; CheckMate 141 ClinicalTrials.gov number, NCT02105636 .).

Objectives. We examined the effects of 2 worksite health-promotion interventions (compared with a health-education control) on older workers’ healthy behaviors and health outcomes. Methods. We conducted a prospective, randomized controlled trial with 423 participants aged 40 years and older. Participants were categorized into 3 study arms: the COACH intervention combined Web-based risk assessments with personal coaching support, the RealAge intervention used a Web-based risk assessment and behavior-specific modules, and a control group received printed health-promotion materials. Participants were assessed at baseline, 6 months, and 12 months. Random-effects modeling controlled for baseline stage of change for all behaviors of interest in all groups. Results. At 6 and 12 months, COACH participants showed significantly increased fruit and vegetable consumption (P = .026; P < .001) and participation in physical activity (P = .05; P = .013), and at 12 months they showed decreased percentage of energy from fat (P = .027). RealAge participants showed significantly decreased waist circumference at 6 and 12 months (P = .05; P = .018). Conclusions. COACH participants were twice as likely to use the COACH intervention as RealAge participants were to use the RealAge intervention. COACH participants experienced twice the number of positive outcomes that control participants experienced.

Objective The D1 model that was developed to predict US societal preferences for EQ-5D health states addressed several important conceptual and statistical issues. However, it has been criticized for being too complex, failing to account for the nonnormal distribution of health state values, and the transformation of preferences for worse-than-death health states before estimation. This research was conducted to develop an improved model for predicting median preferences for EQ-5D health states for the US population. Methods Probability-weighted least absolute deviations regression was used to fit models to the time trade-off data collected in the US Valuation of the EQ-5D Health States study. No transformation was applied to the values for states considered worse than death. Several model specifications that differed with respect to explanatory variables were evaluated using two-sample cross-validation. Results The best-fitting model included only fixed effects for moderate or severe problems in each of the 5 EQ-5D dimensions and excluded a constant. This specification yielded rank correlations between observed and predicted values and median observed and predicted values of 0.635 and 0.991, respectively, as well as a median absolute error of 0.026. The predicted median preferences ranged from 1.00 for full health, to –0.81 for the worst possible health state. Conclusions Due to its simplicity and robustness, a median model is superior to other models for predicting US population preferences for EQ-5D health states. The predictions of this model are suggested for use in applications that require US societal health state values.

Introduction Although the Sexual Encounter Profile (SEP) and International Index of Erectile Function (IIEF) are frequently used to measure erectile dysfunction (ED) treatment outcomes, stopwatch-assessed duration of erection is a new, objective, and potentially useful endpoint of ED treatment effect. Aims To assess the validity and reliability of stopwatch-assessed erection duration against responses to SEP items 2 (SEP-2) and 3 (SEP-3) and IIEF scale scores. Methods Data were taken from a multi-center trial of vardenafil for the treatment of ED. Patients were randomized to vardenafil 10 mg or placebo for 4 weeks. After a 1-week washout period, patients received the alternate therapy for an additional 4 weeks. An electronic diary was used to record information about sexual attempts. The duration of erection was measured using a stopwatch and transcribed into the diary. The SEP was completed following each sexual attempt, and the IIEF was completed at the end of each treatment period. Main Outcome Measures Mean and median values of erection duration, mean SEP-2 and SEP-3 success rates, and scores for each of the 5 IIEF scales were calculated. Results At baseline, correlations of median erection duration with the 5 IIEF scale scores ranged from 0.06 to 0.53, while correlations with mean SEP-2 and SEP-3 success rates were 0.66 and 0.49, respectively. Compared with the other measures, mean and median values of erection duration were less sensitive to differences between placebo- and vardenafil-treated patients and less responsive to clinical change associated with treatment crossover. However, mean erection duration exhibited a good level of reliability (intraclass correlation coefficient=0.72, P Conclusions This study provides evidence for the validity and reliability of stopwatch-assessed duration of erection. Our findings suggest that erection duration is suitable for use as a unique endpoint in ED treatment-efficacy trials conducted for phosphodiesterase type 5 inhibitors.